Recent evidence demonstrates that interactions between different integrins that are present on the cell surface can strongly influence the adhesive function of individual receptors. In this report, we show that Chinese hamster ovary cells that express the integrin αvβ3 in the absence of α5β1 demonstrate increased adhesion and migration on fibrinogen. Furthermore, αvβ3-mediated adhesion to fibrinogen is not augmented by the soluble agonist, MnCl2, suggesting that αvβ3 exists in a higher affinity state in these cells. De novo expression of wild-type α5β1 negatively regulates αvβ3-mediated adhesion and migration. This effect is not seen with expression of a chimeric α5β1 integrin in which the cytoplasmic portion of the α5 integrin subunit is replaced by the cytoplasmic portion of the α4 integrin. In addition, it does not require ligation of α5β1 by fibronectin. Cells that express a constitutively active β3 integrin that contains a point mutation in the conserved membrane proximal region of the cytoplasmic tail, D723R, are resistant to the effect of α5β1 expression. These data provide additional evidence of "cross-talk" between the integrins α5β1 and αvβ3, and support the idea that α5β1 regulates αvβ3-mediated ligand binding. This provides a relevant biological mechanism whereby variations in α5β1 expression in vivo may modulate activation of αvβ3 to influence its adhesive function.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology